Building a tumour in virtual reality allows us to see information about the behaviour, location and characteristics of tumour cells all at the same time. This will help us understand more about tumours and begin to answer questions that have eluded cancer scientists for many years.

Professor Greg Hannon, Principal investigator

Their project

Background

To fully understand cancer, scientists need to know everything about a tumour – what types of cells are in it, how many there are and where they are located in the tumour.

Having such a detailed picture of a tumour would allow scientists and doctors to develop new ways to diagnose and treat the disease, and new ways to stop it spreading and coming back.

But getting such an accurate, precise picture of tumours is extremely difficult to do. So difficult that it’s not been done before.

Professor Greg Hannon and his team of scientists, computer scientists and virtual reality experts from England, Canada, Switzerland and the US aim to change this.

Their Grand Challenge project aims to build a 3D tumour that can be studied using virtual reality and which shows every single different type of cell in the tumour.

The Research

Combining established techniques, including DNA sequencing and imaging, with new technology they will invent and develop, the team will study high-quality breast cancer samples available to them which were collected from women involved in the METABRIC study.

They aim to gather thousands of bits of information about every single cell in a tumour – from cancer cells to immune cells – to find out what cells are next to each other, how they interact with and influence each other, and how they all work together to help tumours survive and grow.

They will then take all the information they collect about the cells in a tumour and use it to construct a 3D version that can be studied using virtual reality.

Using virtual reality will allow scientists to immerse themselves in a tumour, meaning they can study patterns and other characteristics within it, in entirely new ways that aren’t possible in 2D. It will also allow multiple doctors and scientists to look at a tumour at the same time, meaning people at opposite ends of the country, and with different areas of expertise, can work together to help diagnose and treat patients better.

The Impact

By developing an entirely new way to study breast cancer, this team hope to change how the disease is diagnosed, treated and managed.

Ultimately, it could improve how women with breast and other types of cancer are classified, which would improve their treatment and help more people survive the disease.

Project update - Year one

The team has already made substantial and promising advances since they started work in May 2017. At the CRUK Cambridge Institute, they have established a central laboratory that will house the cutting-edge imaging equipment and technologies the team is using and developing, and act as the main project hub for sample analysis.

In the first year, the team was committed to getting the VR technology up and running, recruiting a team of VR developers, including programmers and 3D artists, to work alongside the core team. This partnership has allowed experts from different fields to work closely together to design a system that is both state of the art and easy to use by scientists across the world.

The team has successfully produced the first 3D proof-of-principle model of early breast cancer, which was plugged into the VR headset and viewed by multiple users at the same time – a significant milestone. The team will now continue to improve their sample analysis in preparation for uploading real patient data into the VR technology for the very first time.

Professor Greg Hannon is internationally recognised for his contributions to small RNA biology, cancer biology and mammalian genomics. He has a long history in the discovery of cancer genes and he has developed widely used tools and strategies for manipulation of gene expression in mammalian cells and animals, including generating genome-wide shRNA libraries that are available to the cancer community.

He has a long history of collaboration and technological innovation, which will continue in his role as the PI on the Grand Challenge.

Professor Sir Shankar Balasubramanian is the Herchel Smith Professor of Medicinal Chemistry in the Department of Chemistry and Senior Group Leader at the Cambridge Institute in the University of Cambridge. He specialises in nucleic acids chemistry and is a co-inventor of Solexa-Illumina next generation sequencing and epigenetic sequencing.

His primary contribution to the Grand Challenge will be on the detection and analysis of nucleic acids.

Professor Bernd Bodenmiller

Title: Assistant Professor of Quantitative Biology

Country: Switzerland

Organisation: University of Zürich

Discipline: Systems Biology

Professor Bernd Bodenmiller studied Biochemistry in Bayreuth and at ETH Zürich, where he obtained his PhD with R. Aebersold. . For his postdoctoral training, he joined the laboratory of G. Nolan at Stanford University, developing methods for signaling network analysis by mass cytometry. Mass cytometry allows to quantify 135 proteins at the single cell level. In 2013 he became ERC Assistant Professor at the University of Zürich. There his group developed highly multiplexed tissue imaging by mass cytometry and algorithms for downstream data analyses.

In the Grand Challenge these methods will be used to generate at subcellular resolution three dimensional profiles of protein distribution and signaling activity.

Carlos Caldas is Professor of Cancer Medicine at the University of Cambridge and directs the Breast Cancer Functional Genomics Laboratory at the CRUK Cambridge Institute. He is the Director of the Breast Cancer Programme at the CRUK Cambridge Cancer Centre. His laboratory is focused on characterizing the clonal and cellular heterogeneity of breast cancers and how this affects response to therapy and outcomes, on creating explant models that mimic this heterogeneity and their use for drug testing, and on developing tools to monitor the evolution of breast cancers in space and time.

Carlos’s main contribution to the Grand Challenge will be analysing the unique sample sets accrued in these studies as the primary targets for building 3D tumour maps and how this information will be used as a clinical biomarker

Dr Dario Bressan

Title: Research Associate

Country: UK

Organisation: Cancer Research UK Cambridge Institute

Discipline: Cellular and Molecular Biology

Darrio Bressan graduated in Molecular Biology and Neurobiology from the Scuola Normale Superiore of Pisa, Italy, in 2008. He then moved to the USA, where he obtained a PhD from Cold Spring Harbor Laboratory, NY, working with Dr Greg Hannon. Since 2014, Darrio has been a research associate at the CRUK Cambridge Institute.

His role in the Grand Challenge will be to integrate different types of cellular analysis with 3D imaging in order to produce coherent maps of tumours, and visualise them in an interactive way.

Professor Johanna Joyce

Title: Tenured Faculty, University of Lausanne

Country: Switzerland

Organisation: Ludwig Institute for Cancer Research, University of Lausanne

Discipline: Tumour Biology

Johanna Joyce was recruited to the Ludwig Institute of Cancer Research at the University of Lausanne, Switzerland in 2016. Prior to that, she led a lab at Memorial Sloan Kettering Cancer Center, New York, USA where she was promoted to tenured Full Member and Professor. The Joyce lab investigates the tumour microenvironment of primary cancers and metastatic disease, and in determining the critical influence that non-cancerous immune and stromal cells have on tumour progression and therapeutic response.

Professor Joyce will focus on addressing these important questions in breast cancer as part of the IMAX Grand Challenge team.

Dr Nicholas Walton

Title: Science and Technology Facilities Council Research Fellow

Country: UK

Organisation: Institute of Astronomy, University of Cambridge

Discipline: Astronomy

Dr Nicholas Walton is a research astronomer at the Institute of Astronomy, University of Cambridge. He is interested in understanding the formation and evolution of our Milky Way and the hunt for planets outside of our solar system. He is currently a member of the ESA Gaia science team, and in Cambridge, leads the development of the exoplanet analysis system for ESA's upcoming planet hunter mission, PLATO. Before Cambridge he was at the Royal Greenwich Observatory, La Palma and gained a PhD from Imperial College, London.

Within the Grand Challenge team he is responsible for developing the advanced image analysis techniques to segment, align and initially characterise the cells and structures in the IMAX raw image data.

Owen Harris

Title: Virtual Reality Designer

Country: Republic of Ireland

Organisation: Súil Design

Discipline: Virtual Reality, Game Design

Owen Harris is a designer, programmer, artist and writer. He teaches Game Design in DIT and regularly speaks all over Ireland and Europe. He is a founder of Imirt, an organisation set up to improve the quality and visibility of Irish games, and runs the local community game design event dubLUDO. Owen is obsessed with virtual reality, playfulness and the intersection of technology and wellbeing. When not working on DEEP, a VR mental health game, he builds VR experiences and games for others. His mission is to bring about an increased awareness of the value of playfulness in everyday life.

For the Grand Challenge Owen heads the Virtual Reality team. Working with Flaminia Grimaldi, Dario Bressan and Robby Becker, the team is building a cutting edge virtual lab to explore cancer in a brand new way.

Professor Sam Aparicio

Title: Nan & Lorraine Robertson Chair in Breast Cancer Research at UBC, Head of the British Columbia Cancer Agency Department of Breast and Molecular Oncology

Country: Canada

Organisation: University of British Columbia, British Columbia Cancer Agency

Discipline: Breast Cancer Biology

Professor Samuel Aparicio is the Nan & Lorraine Robertson Chair in Breast Cancer Research UBC, chair of the BC Cancer Agency Department of Breast and Molecular Oncology in Vancouver, Canada and Fellow of the Royal Society of Canada. He has most recently conducted foundational work on methods for studying the evolution of human cancers using next-generation sequencing approaches and single cell sequencing methods. Dr Aparicio is also working to develop quantitative measures of clonal fitness in patients, including methods for single cell genome sequencing and patient derived xenograft models of human cancer.

His role in grand challenge is leader of the Canadian contribution to the GC, focus on single cell genomics as an approach to fitness and cellular dynamics, quantitative methods and visualization.

Professor Simon Tavaré

Title: Director, CRUK Cambridge Institute

Country: UK

Organisation: Cancer Research UK Cambridge Institute

Discipline: Computational Biology

Professor Simon Tavaré spent 25 years in academia in the US before returning to the UK in 2003, where he is a Professor in the Department of Applied Mathematics and Theoretical Physics at the University of Cambridge. His research interests include computational biology, statistics and inference for stochastic processes, particularly approximate Bayesian computation. Since 2013 he has been Director of the Cancer Research UK Cambridge Institute, where his research group focuses on statistical bioinformatics and cancer evolution.

Simon will lead the statistical analysis aspects of the Grand Challenge project.

Xiaowei Zhuang is the David B. Arnold Professor of Science at Harvard University and an investigator of the Howard Hughes Medical Institute. Her lab develops advanced imaging technologies, in particular single-molecule and super-resolution imaging methods, and applies these methods to biological studies.

As a member of the CRUK Grand Challenge Team, she will use MERFISH, a single-cell transcriptome imaging method developed in her lab, to help produce the three-dimensional cell atlas of breast tumors and their host environments. Zhuang is a member of the US National Academy of Sciences and the American Academy of Arts and Sciences, a foreign member of the Chinese Academy of Sciences and the EMBO, a fellow of the American Physical Society, and an honorary fellow of the Royal Microscopical Society.

Ed Boyden is Professor of Biological Engineering and Brain and Cognitive Sciences at the MIT Media Lab and the MIT McGovern Institute. His group develops tools, such as optogenetics and expansion microscopy, for analysing and repairing complex biological systems such as the brain, and applies them systematically to understand and repair these systems. Amongst other recognitions, he has received the Breakthrough Prize in Life Sciences 2016, the BBVA Foundation Frontiers of Knowledge Award 2015 and the Grete Lundbeck Brain Prize 2013 for his work.

His role in the Grand Challenge is to develop optimized forms of expansion microscopy multiplexed analysis of cancer.

Dr Sohrab Shah

Title: Canada Research Chair in Computational Cancer Genomics

Country: Canada

Organisation: The University of British Columbia

Discipline: Computer scientist

Dr Sohrab Shah received a PhD in computer science from UBC in 2008 and was appointed as a Principal Investigator to The BC Cancer Agency and the University of British Columbia in 2010. He holds the Canada Research Chair in Computational Cancer Genomics, and is the recipient of both a Michael Smith Foundation for Health Research Career Investigator Award and a Terry Fox Research Institute New Investigator Award. His research focuses on understanding how tumours evolve over time through integrative approaches involving genomics and computational modeling. Dr Shah has pioneered computational methods and software for inference of mutations in cancer genomes as well as deciphering patterns of cancer evolution which have been widely disseminated internationally.

Elaine Chapman

Title: Patient Advocate

As a cancer survivor and the Lead Cancer Nurse at Addenbrooke’s hospital in Cambridge Elaine is very passionate about changing the face of cancer through both research and patient care. She sees her role as one of "championing the needs of our patients, to improve their experience of care and supporting our cancer teams in delivering the best outcomes through research and evidence."

She is excited to be working with Carlos, Greg and the wider team in this "wonderful opportunity to represent my peers with cancer" and is looking forward to using her own experience to bring their findings to a wider public and patient audience.

Lynn Dundas

Title: Patient Advocate

Lynn was a lecturer working with Disaffected and Special Need teenagers but following her recovery from cancer, she now spends her time volunteering for cancer charities and making time to enjoy life. Lynn’s role within the Grand Challenge team is to provide the link to the patients and give a patient perspective as she says: “having a greater understanding of cancer is very important for a patient’s well-being when facing such a life changing event.

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